Exhibit 99.1

Preclinical Activity of irreversible menin inhibitor, BMF-219, in Chronic Lymphocytic LeukemiaPriyanka Somanath, PhD1, Daniel Lu, MS 1 Brian Law, BS 1, Lekha Kumar, MS1, Tenley Archer, PhD, Tripta Rughwani, MS, Taisei Kinoshita, PhD1, Mini Balakrishnan, PhD1 and Thomas Butler, MSc MBA1,1Biomea Fusion, Inc. Redwood City, CAIntroductionMenin is a scaffold protein that drives oncogenic function through transcriptional modulation directed by its various cofactors.A previous report demonstrated that menin regulates a distinct set of gene targets independent of its function with the MLL proteins in hematopoiesis and is essential for B-cell maturation (Li et al.Blood.2013;122(12):2039-46.).Chronic Lymphocytic Leukemia (CLL) is a disease of malignant B lymphocytes, for which standard-of-care agents are generally well tolerated; however, CLL patients with certain genetic backgrounds demonstrate inferior outcomes to these regimens.Secondary Lymphatic Organs Bone Marrow (Antigen-dependent)Germinal Activated Center (GC) post-GC y B-cell B-cellSmall Plasma Pre-pro B Pro-B1 Pro-B2/ Large pre-B Immature Mature Mature Mature Pre-B pre-B B B B B Cell Memory B-cellALL MCL DLBCL MMFL CLLBL MZL WMMenin dependent functionConfirmed BMF-219 activityA major driving feature of CLL is overexpression of the anti-apoptotic marker, BCL2. We previously reported the ability of BMF-219, a selective, covalent menin inhibitor, to downregulate the expression of BCL2 in acute leukemia cells.Additionally, we have reported the synergy of BCL2-targeted agent, venetoclax, with BMF-219 in potent cell killing of diffuse large B-cell lymphoma (DLBCL) preclinical models, prompting our exploration of BMF-219 activity in CLL.Here, we provide the first preclinical evidence for menin as a therapeutic target in CLL, by demonstrating high potency of BMF-219 against a diverse collection of CLL patient specimens.MethodsA comprehensive panel of CLL samples isolated from patients with Rai Stages 1 to 3 disease, including relapsed or refractory disease, were cultured ex vivo in the presence of BMF-219 or a clinical reversible menin inhibitor to assess the antileukemic activity of the compounds.ResultsRelative Gene Expression – BMF-2191.2BCL2 MYC HOXA91.0 Figure 1. BMF-219 elicits >90% reduction of BCL2 transcript at 24Control 0.8 expression)hours post-treatment in MOLM-13DMSO 0.6 AML cells. HOXA9 and MYC gene(mRNA tonge expression was also significantly0.4- Cha Relative reduced by >90%. Fold change was Fold 0.2 calculated relative to vehicle control.0.0DMSO BMF-219 BMF-219500 nM, 24 1 M, 24 hrsBMF-219 achieves > 98% cell lethality against diverse CLL ex vivo modelsBMF-219 (1.1uM)A Clinical Reversible B100 Menin Inhibitor (1.1 uM) 1 0 0 on Venetoclax (0.8 uM) *ti 80 7 5 hib i60 Inhibitionn 5 0I hth40t ow 2 520 G rGrow% 0% 0-20 -2 5Stage 1 Stage 2 Stage 2 Relapsed Stage 3al al al 1 el S M 1 1 3 3 m m m1D A T C H T TM 5 5 r r r y q RA T W A T P T P o o o om 3 , K 1 , ON N N i s 1 2 H N T r1 C y T Rai Binet Stage m O i s o NT rCytogenetic BackgroundClinical samples with progression after prior treatment with bendamustine or ibrutinibD EC BM-301 BM-302 BM-303125 125 125 n 100 o n n o 100 i o 100 t i ib i 7575 hibit 75 nh 50 nhibiti II In25 50 50 w th th0 25 ow 25 ro G -25 Growth Gr% 0 0% -50 % -75 -25 -250.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10Compound Concentration (mM) Compound Concetration (mM) Compound Concentration (mM)BMF-219 Clinical Reversible ibrutinib BMF-219 Clinical Reversible BMF-219 Clinical Reversible ibrutinib Menin Inhibitor Menin Inhibitor Menin InhibitorFigure 2. Growth inhibition of CLL patient-derived PDX samples treated with BMF-219 or a clinical reversible menin inhibitor after 6 days of treatment. Percentage growth inhibition at 1.1 mM BMF-219, 0.8 mM venetoclax and 1.1 mM clinical menin inhibitor are plotted for the PDX samples, as grouped by genetic background (A) or Rai-Binet Stage where data is available (B). Representative dose response curves for BMF-219 or clinical reversible menin inhibitor are shown for PDX samples from CLL patients displaying clinical profiles of progression after prior therapy with bendamustine (C) or ibrutinib (D), or ibrutinib pretreated and subsequently progressed on ibrutinib and venetoclax (E). IC50 values are summarized in Table 1. Each data point represents average of at least two replicate values. (*Venetoclax concentration set as standard for positive control). Ibrutinib IC50 determined as a standalone experiment.Table 1. Clinical Profiles of CLL Patient Samples and Response to BMF-219Rai Binet Stage BMF 219 BMF 219 % Max Sample Mutation Cytogenetics Prior Treatment IC (mM) Inhibition50Bendamustine (responded, thenBM-301 ATM Normal Stage 2 (Relapsed) 0.373 98.7 progressed) BM-302 NOTCH1 Normal Ibrutinib (responded, then progressed) Stage 2 (Relapsed) 0.332 99.7 Ibrutinib (responded), (post-collection: BM-303 TP53 N/A ibrutinib and venetoclax- responded, Stage 1 0.285 99.8 then progressed) 44, XX, add(3)(q21), -5, add(6)(p12), +11, der(11;13)(q10;q10), -13,t(15;18)(q15;q21), BM-304 None or N/A Ibrutinib (responded) Stage 1 0.104 99.9 add(16)(p13.3), add(17)(p11.2) [cp15]/46, XX [6] BM-305 WT1 Normal Rituximab/Ibrutinib (responded) Stage 2 0.384 100BM-306 TP53 Normal Ibrutinib (responded, no progression) Stage 3 0.380 10047, XY, +12, t(14;19)(q32;q13.3), Rituximab/MethylprednisoloneBM-307 KRAS, KMT2A, TET2 N/A 0.145 99.5 t(16;20)(p13.3;q13.1) [13]/46, XY [7] (responded), ibrutinib46~47, XY, del(6)(q13q25),Rituximab/Ibrutinib (responded,BM-308 None or N/A dic(7;21)(q31;p13), add(11)(q13), Stage 2 0.359 99 continuing) del(13)(q12q14), +2mar, inc [cp4]/46, XY [3]BM-309 None or N/A Normal Ibrutinib (responded) Stage 3 0.331 100BM-310 None or N/A Normal Ibrutinib (responded) N/A 0.357 99 BM-311 NOTCH1, ATM N/A N/A Stage 2 (Relapsed) 0.359 100 BM-312 None or N/A N/A N/A N/A 0.384 100BMF-219 exhibits higher ex vivo potency compared toStandard-of- Care AgentsBMF 219 %BMF 219 Max Ibrutinib Bendamustine Idelasib Sample Mutation IC (mM) Inhibition IC (mM) IC (mM) IC (mM)50 50 50 50BM-301 ATM 0.373 98.7 14.8 15.6 8.91BM-302 NOTCH1 0.332 99.7 N/A N/A N/ABM-303 TP53 0.285 99.8 29.1 31.9 37.2 BM-304 None or N/A 0.104 99.9 N/A N/A N/A BM-305 WT1 0.384 100 34.8 17.1 35.7 BM-306 TP53 0.38 100 24.1 6.65 2.21KRAS, KMT2A,BM-307 TET2 0.145 99.5 18.3 16.1 0.271BM-308 None or N/A 0.359 99 26.7 15.7 22.7 BM-309 None or N/A 0.331 100 29.0 25.2 38.1 BM-310 None or N/A 0.357 99 12.4 6.84 1.67BM-311 NOTCH1, ATM 0.359 100 29.1 32.2 35.7 BM-312 None or N/A 0.384 100 N/A N/A N/ATable 2. BMF-219 potency as determined by IC50 values in comparison with standard-of-care agents for CLL. CLL ex vivo patient samples were cultured with BMF-219 for 6 days to determine IC50 values. IC50 values for Ibrutinib (BTK inhibitor), bendamustine (alkylating agent) and idelasib (PI3K inhibitor) were experimentally determined as standalone experiments in these patient models.Conclusionsâ–ª BMF-219 demonstrated high potency, achieving >98% cell lethality at 1.1 mM exposure in all CLL patient samples tested, with IC50 values in the range of 0.1 to 0.38 mM, similar to BMF-219 potency in AML and DLBCL ex vivo models.â–ª Specimens isolated from patients with clinical profiles containing high-risk genetic backgrounds associated with inferior outcomes to standard therapy, such as mutations in TP53 and NOTCH1, and chromosomal aberrations such as del(13q), trisomy 12 and complex karyotype, exhibited high sensitivity to BMF-219 treatment.â–ª BMF-219 was also highly effective against patient samples with clinical profiles of resistance to bendamustine or ibrutinib therapy.â–ª A clinical reversible menin inhibitor demonstrated no significant activity across all patient samples tested, with incalculable IC50 values and <15% reduction in cell viability at 1 mM exposure.â–ª Collectively, our data demonstrate the potent preclinical activity of BMF-219 against CLL patient specimens harboring various mutational and cytogenetic backgrounds, including categories of high unmet need, highlighting the unique potential of covalent menin inhibition as a novel therapeutic option for patients with CLL.Referencesâ–ª Li, BE., Gan, T., Meyerson, M., et al. Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells. Blood (2013) 122 (12): 2039–2046.â–ª Somanath, P., Lu, D., Law, B. et al. Novel Irreversible Menin Inhibitor, BMF-219, Shows Potent Single Agent Activity in ClinicallyRelevant DLBCL Cells. Blood 2021; 138 (Supplement 1): 4318.â–ª Wu, G., Yuan, M., Shen, S. et al. Menin enhances c-Myc-mediated transcription to promote cancer progression. Nat Commun 8, 15278 (2017).

Exhibit 99.2

Menin is a scaffold protein, encoded by the gene MEN1, that has been recently . recognized for its role in Type 2 Diabetes Mellitus (T2DM) as a key regulator of b-cell proliferation. Men1 knockout mice demonstrate increased B-cell mass generation (Yang et al., 2010) Menin inhibition has previously been shown to improve glycemic control in high fat induced diabetic mice (Ma et al., 2021). Men1-excised mice do not develop hyperglycemia in a Streptozotocin-(STZ) induced rat model, which is a model for impaired beta-cell function and insulin production, demonstrating the role of menin in glycemic control. BMF-219 is an orally bioavailable, selective, covalent menin inhibitor that elicits a broad impact on the complexes surrounding menin that also direct its biological function. Herein, we report the first evidence that BMF-219 restores glycemic control in Zucker Diabetic Fatty (ZDF) Rat and Streptozotocin-induced Rat (STZ) models of T2DM, with prolonged glycemic control two weeks after dosing in ZDF rats.MethodsZDF rats were treated daily with BMF-219, vehicle, or pioglitazone for 16 days monitored for an additional two weeks post-treatment, until Day 29. STZ rat models were induced through pre-treatment of animals on a high-fat diet with low doses streptozotocin at day -14 and day -7 prior to starting treatment at Day 0 until Day ZDF and STZ rats were monitored for fasting blood glucose levels, oral glucose tolerance test (OGTT), insulin and C-peptide levels, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), blood lipemic levels and body weight according the schematic for each model below. ZDF rats were analyzed for indicated readouts 15 days post-treatment for OGTT at day 29, and serum insulin and C-peptide at dayDay: 0 8 16 21 29ZDF Rat Model Daily oral dosing (QD) Drug wash outTreatment groups (n=10/group): last dose1. Vehicle2. BMF-219 175 mg/kg Rats monitored for the following parameters through dosing and 3. Pioglitazone 30 mg/kg washout phases include: Body weight, fasting blood glucose, blood insulin, C-peptide, and OGTTDay: -14 -7 0 8 16STZ Rat ModelSTZ Pre-TreatmentDaily oral dosing (QD) (β-cell mass depletion) first dose last doseTreatment groups (n=10/group):1. VehicleRats monitored for the following 2. BMF-219 175 mg/kg parameters through dosing 3. Pioglitazone 30 mg/kg include: OGTT, blood glucose levelsBMF-219 demonstrates significant glycemic control in ZDF RatsOGTT, Day 15 B Blood Glucose (4hr fasting) C Insulin (4hr fasting) D C-peptide (4hr fasting)A 600 *    p<0.05 vs Vehicle 10** p<0.01 vs Vehicle 400 ** p<0.01 vs Vehicle *** p<0.001 vs VehicleL) 6000 ** p<0.01 vs Vehicle*** p<0.001 vs Vehicle * p<0.05 vs Vehicle * p<0.05 vs Vehicle * p<0.05 vs VehicledL) g/m 8 SEM ± g/ 300 ( n g/dL) (m 6 an SEM ** lin * 4000OGTT, Area Under the Curve (AUC) Mem M 400 ± , *( E cose 200 * su 4 *** M)80000 u in (p*** p<0.001 vs Vehicle S ** ** gl ** ** ** Mean de 2000ï,± 54% reduction ood 100 2 i ptcose 60000 B l erum peu n ** **S -l 0 C** 0 0G Mea 200 * 40000 *** ***** ** p<0.01 vs Vehicle** *** ** *** p<0.001 vs Vehicle* ** 20000 E Non-fasting glucose Blood 60000 Vehicle Pioglitazone BMF-219 (mg/dL) (30 mg/kg) (175mg/kg) 4000 15 30 60 90 120 SE ** ** **ï,± ***Minutes Mean 200Vehicle Pioglitazone (30 mg/kg)0BMF-219 (175mg/kg) Day -3 Day 1 Day 8 Day 14Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg)Figure 1. BMF-219 significantly reduces blood glucose levels and alters serum insulin and C-peptide levels in ZDF rats. ZDF rats treated with BMF-219, pioglitazone or vehicle for 16 days were evaluated at various time points. Day 15 OGTT results are shown as time course and AUC (A). Day 17 fasting blood glucose levels (B), fasting insulin (C), and fasting C-peptide (D) are shown. Non-fasting blood sugar was measured weekly on Days -3, 1, 8 and 14 (E). Statistical significance was calculated for treatment groups in comparison with vehicle control.BMF-219 displays strong glycemic control two weeks after last dose in ZDF RatsBlood Glucose (4hr fasting) Insulin (4hr fasting) C-peptide (4hr fasting)OGTT, Day 29 75% glycemic control B C DA maintained on day 29 post- 600 ** p<0.01 vs Vehicle 15 ** ** p<0.01 vs Vehicle ** p<0.01 vs Vehicle800 * p<0.05 vs Vehicle * p<0.05 vs Vehicle 6000 ** * p<0.05 vs Vehicledosing compared to day 15 dL) / *g(m 400 mL) M 10 M) EM 4000S ** SE ( pL) ng/ ( SEM± ï,± e n id ± cose lu ean * ean *OGTT AUC on day 29 g 200 ** M 5 pept **600 M—Mean 2000 d Insuli o * C(mg/d 100000 Bl o EMS 0 0 0 80000 on Day 17 on Day 31 on Day 17 on Day 31*p<0.05 vs Vehicle on Day 17 on Day 31ï,± 4001 day after 15 days after 1 day after 15 days after 1 day after 15 days after lucose 60000 * last dose last dose last dose last dose last dose last dose* *G 40000 Pioglitazone BMF-219 Pioglitazone BMF-219 Pioglitazone BMF-219 * Vehicle Vehicle VehicleMean 200 * (30 mg/kg) (175mg/kg) (30 mg/kg) (175mg/kg) (30 mg/kg) (175mg/kg) lood * 20000B * * p<0.05 vs Vehicle 0Vehicle Pioglitazone BMF-219 Figure 2. BMF-219 maintains significant impact on blood glucose, insulin and C-peptide0 (30 mg/kg) (175mg/kg)levels during drug washout (two weeks after last dose). ZDF rats treated with BMF-219,0 15 30 60 90 120 pioglitazone or vehicle control for 16 days were monitored for blood glucose levels by OGTT Minutes on day 29, ~2 weeks after administration of the last dose, displaying an AUC reduction ofVehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg)40%, (p<0.05) (A), and on day 31 monitored for 4-hour fasting blood glucose (B), fasting serum insulin (C), and fasting C-peptide levels (D). Statistical significance was calculated for treatment groups in comparison to vehicle control.BMF-219 achieves marked glycemic control in STZ-induced Rats 800 B STZ + HFD modelA OGTT, Day 17 Non-fasting Glucose Vehicle dL) OGTT AUC, Day 15 Pioglitazone (30 mg/kg)/ 800 g 600 100000 41% reductionm M BMF-219 (175mg/kg)( SE 80000se /dL) 600oï,± 400 60000u c n * mgGl 40000(400 d Mea SE200 * * 20000loo *ï,± nB * * 0 ea 200* p<0.05 vs Vehicle Vehicle Pioglitazone BMF-219(30 mg/kg) (175mg/kg) M00 15 30 60 90 120 *p<0.05 vs Vehicle0Minutes -7 -6 -5 -4 -3 -2 -1 1 8 14DaysVehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg)STZ pre-treatment TA dosing startFigure 3. BMF-219 strongly reduces blood glucose levels in STZ-induced rats. STZ rats pretreated with streptozotocin for 14 days (see methods) were treated with BMF-219, pioglitazone or vehicle control for 16 days. Blood glucose was measured by OGTT on Day 17 and displayed an AUC reduction of 41%, (p<0.05) in BMF-219 treated rats only with no change to the pioglitazone treated group (A). Non-fasting glucose levels were measured daily during model establishment (STZ treatment) and weekly during treatment with BMF-219, pioglitazone or vehicle control, displaying reduction of glucose levels in BMF-219 treated rats throughout the duration of treatment (B).BMF-219 increases insulin sensitivity in ZDF ratsA HOMA-IR (4hr fasting) B HOMA-IR (non-fasting)150 400*** p<0.001 vs Vehicle*** p<0.001 vs Vehicle 300100200(ng/mL) *** ***50 *** ***100 *** ***0 0Day 1 Day 8 Day 14Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg)Figure 4. Measurement of HOMA-IR in rats treated with BMF-219 for 16 days. ZDF rats treated with BMF-219, pioglitazone or vehicle were analyzed for HOMA-IR fasting at day 17(A) or non-fasting (B) and values were compared to vehicle control to calculate statistical significance.BMF-219 significantly reduces blood lipemic levels and reduces body weight in treated ZDF ratsA CholesterolC250* p<0.05 vs Vehicle ** p<0.01 vs Vehicle(mg/dL) 200 * Body Weight (g)SEM 150 ** ±    600Cholesterol Mean 100 55050 (g)Serum 500 0 Vehicle Pioglitazone BMF-219 weight 450 (30 mg/kg) (175mg/kg) dy 400B B oTriglycerides3501500300(mg/dL) -7 -5 -3 1 4 6 8 11 13 15 18 20 22 25 27 29 1000 ** p<0.01 vs VehicleSEM Days± Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg)Triglycerides Mean 500 ** Serum ** 0 Vehicle Pioglitazone BMF-219 (30 mg/kg) (175mg/kg)Figure 5. Measurement of cholesterol, triglycerides and body weight in BMF-219 treated rats for 16 days. Cholesterol (A) and triglycerides (B) were measured at Day 17. Body weight was measured daily during treatment and continually monitored two weeks after treatment (C). All groups were treated with vehicle, BMF-219 or pioglitazone and compared to vehicle for statistical analyses. Animals continued to eat a high fat diet until Day 29.Conclusions BMF-219 was tested in rats at clinically relevant exposures. BMF-219 treatment resulted in a significant reduction (~50%) in fasting and non-fasting blood glucose levels, significantly reduced serum insulin and C-peptide levels (p<0.05), and reduced HOMA-IR (p<0.001) after two weeks of treatment in ZDF rats. BMF-219 showed prolonged glycemic control as evidenced by decreased glucose levels during an oral glucose tolerance test on day 15 (AUC reduction of 54%, p<0.001) and on day 29 during the drug washout period (AUC reduction of 40%, p<0.05, ~2 weeks after the last dose) in the ZDF model, indicating durable glycemic control. Strikingly, BMF-219, but not pioglitazone, reduced blood glucose levels by OGTT in STZ animals (AUC reduction of 41%, p<0.05). Significant reductions in blood lipemic levels (p<0.01) and body weight were observed in both models. Collectively, our data indicate the novel and marked potential of BMF-219 as an oral, long-acting treatment for T2DM.References Ma, J. et al. Menin-regulated Pbk controls high fat diet-induced compensatory beta cell proliferation. EMBO Mol Med. 2021;13(5):e13524. Yang, Y. et al. Deletion of the Men1 gene prevents streptozotocin-induced hyperglycemia in mice. Exp Diabetes Res. 2010;2010:876701.

Exhibit 99.3

Oral Menin Inhibitor, BMF-219, displays a significant and durable reduction in HbA1c in a Type 2 Diabetes Mellitus Rat ModelPriyanka Somanath, PhD1,, Sanchita Mourya, MD1, Weiqun Li, PhD1, Brian Law, BS 1, Tenley Archer, PhD, Daniel Lu, MS, Tripta Rughwani, Lekha Kumar, Taisei Kinoshita, PhD1, Mini Balakrishnan, PhD1 and Thomas Butler, MSc MBA1 1Biomea Fusion, Inc. Redwood City, CAIntroduction. diverse Menin is a scaffold protein encoded by the gene, MEN1, that regulates cellular processes in a tissue-context dependent manner. Menin plays a key role in beta-cell proliferation and function, as previously demonstrated though increased beta-cell mass generation in Men1 knockout mice(Ma et al., 2021). The menin-MLL interaction also plays a role in suppressing islet cell growth through control of cell cycle inhibitor expression. Importantly, menin inhibition has been shown to improve b-cell proliferation and glycemic control in high fat-induced diabetic mice (Ma et al., 2021). BMF-219 is an orally bioavailable, selective, covalent menin inhibitor that elicits a broad impact on the complexes surrounding menin, which direct its biological function. Here, we demonstrate the marked potential of an oral menin inhibitor, BMF-219, in achieving durable glycemic control following a short course treatment in a Type 2 Diabetes Mellitus (T2DM) Zucker Diabetic Fatty Rat model.MethodsZucker Diabetic Fatty (ZDF) rats were dosed daily with BMF-219, liraglutide or vehicle for 28 days (n=10 per group) and monitored for an additional 28 days post last dose as shown in scheme below. Group 1 dose (40 mg/kg) was increased to 200 mg/kg on day 17 for rest of the dosing phase. Fasting blood glucose, insulin, C-peptide levels,HbA1c, oral glucose tolerance test (OGTT) and body weight were monitored during and post-treatment.Day: 0 8 15 21 28 43 56Daily oral dosing (QD) Drug wash outGroup 1 dose increased last dose study from 40 to 200 mg/dayTreatment groups (n=10/group): termination1. Vehicle2. BMF-219 40 mg/kg days 1-16, 200 mg/kg days 17-283. BMF-219 85 mg/kgRats monitored through dosing and washout phases: 4. BMF-219 170 mg/kg• Body weight, fasting blood glucose, blood insulin, C-5. Liraglutide 0.2 mg/kg peptide, HbA1c and OGTTResults425SE M 400 Figure 1. Body weight of±ea n ZDF rats during the 28M 375(g)    days of treatment with BMF-219, liraglutide, orht 350 i gw e vehicle control. Data ody 325 represents mean SEM for B the dose group.3001 3 5 8 10 12 15 17 19 21 22 25 28 29 31DaysVehicle 0mg/kg BMF-219 40mg/kg (days 1-16), 200mg/kg (days 17-28) PO BMF-219 170mg/kg PO BMF-219 85mg/kg PO Liraglutide 0.2mg/kg BIDBMF-219 significantly reduces HbA1c and controls blood glucose levels in a 4-week dosing study in ZDF ratsBMF-219 Day 29: 3.5% reductionHbA1c (%)    A. 4-hour Fasting Blood Glucose (mg/dL) * p<0.05 B** p<0.001                **** p<0.0001 15 * p< 0.05800                **** p< 0.0001                M                SE                 600mg/dL)± 10( SEM ean M± 400 an ( %) glucosse c 5 Me 1o d 200 b Alo H B0 0Day 1 Day 8 Day 15 Day 21 Day 29 Day 1 Day 8 Day 15 Day 21 Day 29Vehicle 0mg/kg PO BMF-219 40mg/kg (days 1-16), 200mg/kg (days 17-28) PO QD BMF-219 85 mg/kg PO QD BMF-219 170 mg/kg PO QD Liraglutide 0.2 mg/kg BIDFigure 2. Reduction in fasting blood glucose and HbA1c levels in BMF-219 treated ZDF rats. Rats treated with BMF-219 at indicated doses, liraglutide, or vehicle control were monitored for 4-hour fasting glucose (A) and HbA1c (B) was calculated for treated animals weekly over a 28-day treatment. Changes in blood glucose or HbA1c were compared to vehicle control to calculate statistical significance.BMF-219 displays durable glycemic control over 4 weeks of dosingB Vehicle 0mg/kg4-hour fasting Insulin BMF-219 40 mg/kg PO(days 1-16), 200 mg/kg PO (day 17-28) A OGTT on Day 25 BMF-219 85mg/kg PO10BMF-219 170mg/kg PO900 EM 9Liraglutide 0.2 mg/kg BIDS 8± an 7800 eM 6dL) L), 5g/g/m 4M 700 (n(m E n 3e S uni 2s o± 600 Ins 1 c n0lu aG Day 1 Day 8 Day 15 Day 21 Day 29 Day 43 d Me 500 C 15 days after o last doseo 5000 4-hour fasting C-peptidelB 400 E MS 4000*±a n300 * M e 30000 15 30 60 90 120 M),(p 2000Time (min) d eVehicle 0mg/kg pepti 1000 BMF-219 40 mg/kg (Day 1-16),—CBMF-219 85mg/kg PO 200mg/kg (Day 17-28) PO 0Liraglutide 0.2 mg/kg BID BMF-219 170mg/kg PO Day 1 Day 8 Day 15 Day 21 Day 29 Day 4315 days after last doseFigure 3. BMF-219 exerts strong glycemic control over 28-days of treatment in ZDF rats. OGTT was conducted on day 25 on rats treated with BMF-219 at indicated doses, liraglutide or vehicle control by measurement of blood glucose at 15 and 30 minute intervals up to 2 hours (A). Fasting insulin (B) and C-peptide (C) levels were measured weekly over 28 days in rats treated with BMF-219 at indicated doses, liraglutide, or vehicle control. Insulin and C-peptide levels were also measured on day 43 (15 days after the last dose was administered).BMF-219 maintains a significant reduction of HbA1c two weeks after the last dose*    p<0.05 **    p<0.01 HbA1c (%) ****p<0.0001                15 Vehicle 0mg/kgEM                BMF-219 40mg/kg (days 1-16), S 200mg/kg (days 17-28) PO± BMF-219 85mg/kg PO n 10ae BMF-219 170mg/kg POM), Liraglutide 0.2 mg/kg BID( % c 5 HbA 10Day 29 Day 431 day after last dose 15- days after last doseFigure 4. HbA1c levels measured 2 weeks after administration of last dose in ZDF rats. Rats treated for 28 days with BMF-219 at indicated doses, liraglutide or vehicle control were monitored for HbA1c levels on day 1 and day 15 post-dosing. Drug-treated groups are compared to vehicle control to calculate statistical significance by two-way ANOVA.Conclusions BMF-219 was tested in rats at clinically relevant exposures. All animals tolerated BMF-219 well throughout the study, displaying high activity. BMF-219 mid and high-dose arms showed reduction in fasting blood glucose levels similar to liraglutide. On day 29 (one day after treatment stop), BMF-219 high dose group showed sustained and significant reduction in fasting blood glucose. BMF-219 treatment reduced HbA1c levels by Day 21 of treatment. Absolute amounts were lower than vehicle group by 3.5% (33% reduced from vehicle) and lower than liraglutide group by 1.8% (20% reduced from vehicle) on day 29, and remained reduced throughout the study, including post-treatment. All BMF-219 dose groups showed improved glycemic control by oral glucose tolerance test (OGTT) on day 25, in comparison to vehicle-treated group, with the high dose-treated group showing improved response vs liraglutide. Fasting insulin and c-peptide levels were elevated in BMF-219 treated animals up to the last day of dosing, with the effects lasting well into two weeks post last dose. BMF-219 induced significant reductions in HbA1c at all doses tested, with the effects lasting 15 days after the last dose. Of note, animals in this study, including vehicle group, displayed progressive increase in body weight and fasting blood glucose levels over time, likely from very high food intake. This compromises meaningful data interpretation beyond day 43. Collectively, these data demonstrate the novel long-acting potential of BMF-219 as an oral treatment for T2DM, in maintaining glycemic control after short-term dosing.ReferencesMa, J. et al. Menin regulated Pbk controls high fat diet induced compensatory beta cell proliferation. EMBO Mol Med. 2021; 13(5):e13524.